This article is a clinical study on the different levels of risk factor that are associated with the use of both edoxaban and warfarin among patients. The article is authored jointly by Members of the ‘Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Mycardial Infraction’ (ENGAGE AF-TIMI 48). The purpose of this research was to identify the long-term effectiveness and risk factor of both edoxaban and warfarin when treating individuals with Atrial Fibrillation (AF). In clinical nursing, AF is one of the most prevalent types of cardiac arrhythmia and it is known to affect a significant proportion of the population. Patients who suffer from AF have a great risk factor when it comes to stroke when compared to the rest of the population. For instance, individuals with AF have a 5-7 fold greater risk of suffering from stroke. There are various methods of combating the risk of stroke among patients including thromboembolism via anticoagulation and use of inhibitors such as the edoxaban. In this clinical trial, the goal of the researchers was to “compare Edoxaban, an oral factor Xa Inhibitor with warfarin for stroke prevention in ENGAGE AF-TIMI 48 trial” (Giugliano et al. 2092). This paper is a critique of the clinical study on edoxaban with emphasis on its application to clinical practice.
This clinical study is not isolated when it comes to its objectives. The study is one of several clinical trials that have sought to compare an oral anticoagulant to warfarin whereas issues of stroke-prevention are involved. All the literature that is used in this study borrows heavily from the other three studies that have sought to compare warfarin with oral anticoagulants. Consequently, the literature review that is employed in this study is thorough and it gains credibility from using information from the other three similar clinical trials. The authors are able to prove the efficacy of edoxaban as a stroke-preventive method by using research that has been verified in the past. Edoxaban represents an improvement in Xa inhibitors because it is the most recent one. The clinical trial that is addressed in this study utilizes recent literature on similar clinical trials. The article’s literature indicates that initial assessment trials on the Xa inhibitor had proven that the healthy individuals who volunteered for the trial demonstrated normal levels of pharmacodynamic (PD) and pharmacokinetic (PK) profiles. Furthermore, the volunteers had the option of using any foods that were available to them. The study also points out to the trials where dosages of edoxaban were increased systematically. In another recent development on the clinical trials of edoxaban, it was found that increasing the dosage of edoxaban in a systematic manner triggered some form of bleeding among patients. All these recent literature reviews help in defining the significant steps that have preceded the clinical comparison of edoxaban and warfarin. Therefore, the authors of this study gain credibility from citing recent and processional research on edoxaban. On the other hand, the content of the literature that is reviewed in this study aligns with all the other three clinical studies on the subject. Three of the previous studies that are cited in this article have been aimed at establishing the efficiency of inhibitors as compared to warfarin. In the course of all these reviewed studies, a total of two thousand and nine hundred patients have been involved in the trials out of a sample of more than seventy thousand individuals. Consequently, the inclusion of all the three studies in the literature review of this article adds credibility to this study and makes it a viable point of reference for future studies.
The conceptual framework for this study was in the form of “a three-group, randomized, double-blind, double-dummy trial comparing two dose regimens of edoxaban with warfarin” (Giugliano et al. 2093). This research design enabled the authors of this article to conduct trials in forty-six countries around the world. This model is largely conceptual but it is synonymous with clinical drug trials. In addition, this research model is simplified for the purposes of attaining ‘straightforward’ results as required by this clinical trial. For instance, the study model seeks to calculate the risk levels that are associated with various dosages of edoxaban. The large sample size can be linked to the conceptual framework that is used in this clinical study. Furthermore, the comparative nature of the study’s results makes it necessary for the researchers to use this conceptual framework. In the study’s findings, the researchers indicate that “the median time in therapeutic range for warfarin is 68.4%” (Giugliano et al. 2094). These results are only made possible by the conceptual framework of research that utilizes ‘double-blind, double-dummy’ trial.
The sample for this clinical study included patients who were sourced from forty-six countries across the world. The subjects for the study included individuals who were over 21 years of age. Furthermore, the test subjects were only qualified if they have had a documented case of AF within the last year. The patients were also qualified for the study using the “CHAD risk assessment whereby individuals had to have a score of 2 or higher for the duration of the trial” (Giugliano et al. 2093). The authors of the study also excluded individuals from the study using various disqualifiers including inability to follow rules, reversible AF scenarios, and higher than average risks of bleeding. The sample is quite representative especially in matters concerning the prevalence of AF. The authors of the study are conversant with the prevailing patterns of AF and they employ this knowledge when they are picking the samples for this study. The study also favors the sample population that falls within the age limit of over 75 years. Consequently, the trial is able to concentrate on an important demographic where AF patients are concerned.
The researchers employed various methods and designs in their clinical trial. Each of the selected tested groups was randomized to ensure that the results of the study were free from manipulation. In the group that was administered with edoxaban, the researchers subdivided the group into various categories. Edoxaban dosages were administered in accordance with a patient’s age, weight, and creatinine levels. Furthermore, the levels of warfarin that was administered to patients mostly remained constant although few adjustments were made from time to time. The researchers also administered placebo dosages among some of the patients who took part in the study. Patients “had to have a CHADS2 score ≥ 2 to be included, and key exclusion criteria were creatinine clearance less than 30ml per minute or moderate to severe mitral stenosis….each edoxaban arm was evaluated for non-inferiority compared to warfarin” (Giugliano et al. 2092). The authors of this study have fully explained their data collection methods in relation to the outline of the study. Consequently, the study methodology and analysis is professional and up to par with the standards of clinical trials. The most important goal of any clinical study is to eliminate the margins for error. Even small errors in the clinical studies could be catastrophic to patient safety. It is also important to note that in the case of this clinical study, the expected outcome was bleeding. However, if this bleeding exceeded certain levels it would be harmful to the test subjects. This delicate balance makes this clinical study very sensitive to errors.
The results of this clinical study are hard to dispute due to the manner in which they are presented by the researchers. According to the article, when edoxaban is presented in both low and higher than normal dosages, it does not indicate any inferiority to warfarin. The study’s results declare that “the superiority analysis for prevention of stroke or systemic embolism showed a trend towards superiority for the high dose of edoxaban (HR 0.87, 97.5% CI 0.73-1.04, p-value=0.08) and a negative trend for the low dose of edoxaban” (Giugliano et al. 2099). Nevertheless, it is important to note that the findings of the clinical trial declare edoxaban to be “non-inferior” to warfarin. The use of the phrase ‘non-inferior’ is a veiled attempt by the researchers to declare that edoxaban is only ‘equal to’ warfarin when combating AF. In the article’s discussion, the researchers refrain from making market-oriented comparisons between warfarin and edoxaban. This tactic is effective for the researchers because it prevents the study from being proprietary in nature. In addition, the researchers are able to present a one-sided account of their study without losing their professional stance. It is also important to note that this ENGAGE AF study did not address the pertinent issue of lack of reversal agents that was encountered during preceding clinical trials.
Giugliano, Robert P., et al. “Edoxaban versus warfarin in patients with atrial fibrillation.” New England Journal of Medicine 369.22 (2013): 2093-2104. Print.